ID CAN2_HUMAN Reviewed; 700 AA. AC P17655; A6NDG7; B7ZA96; E7ES58; Q16738; Q6PJT3; Q8WU26; Q9HBB1; DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 6. DT 27-NOV-2024, entry version 254. DE RecName: Full=Calpain-2 catalytic subunit; DE EC=3.4.22.53; DE AltName: Full=Calcium-activated neutral proteinase 2; DE Short=CANP 2; DE AltName: Full=Calpain M-type; DE AltName: Full=Calpain large polypeptide L2; DE AltName: Full=Calpain-2 large subunit; DE AltName: Full=Millimolar-calpain; DE Short=M-calpain; DE Flags: Precursor; GN Name=CAPN2; Synonyms=CANPL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-22. RX PubMed=2852952; DOI=10.1021/bi00421a022; RA Imajoh S., Aoki K., Ohno S., Emori Y., Kawasaki H., Sugihara H., Suzuki K.; RT "Molecular cloning of the cDNA for the large subunit of the high-Ca2+- RT requiring form of human Ca2+-activated neutral protease."; RL Biochemistry 27:8122-8128(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLU-22. RC TISSUE=Astrocytoma; RX PubMed=10944468; DOI=10.1006/bbrc.2000.3282; RA Ye Z., Connor J.R.; RT "cDNA cloning by amplification of circularized first strand cDNAs reveals RT non-IRE-regulated iron-responsive mRNAs."; RL Biochem. Biophys. Res. Commun. 275:223-227(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-22; GLY-68; ARG-476; RP GLN-521; GLN-568 AND GLN-677. RG NIEHS SNPs program; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLU-22. RC TISSUE=Pancreas, Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79, AND VARIANTS GLU-22 AND GLY-68. RC TISSUE=Lymph node; RX PubMed=2539381; DOI=10.1016/s0021-9258(18)83364-6; RA Hata A., Ohno S., Akita Y., Suzuki K.; RT "Tandemly reiterated negative enhancer-like elements regulate transcription RT of a human gene for the large subunit of calcium-dependent protease."; RL J. Biol. Chem. 264:6404-6411(1989). RN [8] RP PROTEIN SEQUENCE OF 2-12. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [9] RP FUNCTION. RX PubMed=17650508; DOI=10.1074/jbc.m609608200; RA Sanchez-Sanchez F., Martinez-Redondo F., Aroca-Aguilar J.D., RA Coca-Prados M., Escribano J.; RT "Characterization of the intracellular proteolytic cleavage of myocilin and RT identification of calpain II as a myocilin-processing protease."; RL J. Biol. Chem. 282:27810-27824(2007). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS). RX PubMed=10639123; DOI=10.1073/pnas.97.2.588; RA Strobl S., Fernandez-Catalan C., Braun M., Huber R., Masumoto H., RA Nakagawa K., Irie A., Sorimachi H., Bourenkow G., Bartunik H., Suzuki K., RA Bode W.; RT "The crystal structure of calcium-free human m-calpain suggests an RT electrostatic switch mechanism for activation by calcium."; RL Proc. Natl. Acad. Sci. U.S.A. 97:588-592(2000). RN [13] RP VARIANT [LARGE SCALE ANALYSIS] GLU-22, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). CC -!- FUNCTION: Calcium-regulated non-lysosomal thiol-protease which CC catalyzes limited proteolysis of substrates involved in cytoskeletal CC remodeling and signal transduction. Proteolytically cleaves MYOC at CC 'Arg-226' (PubMed:17650508). Proteolytically cleaves CPEB3 following CC neuronal stimulation which abolishes CPEB3 translational repressor CC activity, leading to translation of CPEB3 target mRNAs (By similarity). CC {ECO:0000250|UniProtKB:O08529, ECO:0000269|PubMed:17650508}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Broad endopeptidase specificity.; EC=3.4.22.53; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC Note=Binds 7 Ca(2+) ions. {ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by 200-1000 micromolar concentrations of CC calcium and inhibited by calpastatin. CC -!- SUBUNIT: Forms a heterodimer with a small (regulatory) subunit CC (CAPNS1). Interacts with CPEB3; this leads to cleavage of CPEB3. CC {ECO:0000250|UniProtKB:O08529, ECO:0000250|UniProtKB:Q07009}. CC -!- INTERACTION: CC P17655; P04632: CAPNS1; NbExp=6; IntAct=EBI-1028956, EBI-711828; CC P17655; P55212: CASP6; NbExp=3; IntAct=EBI-1028956, EBI-718729; CC P17655; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1028956, EBI-21591415; CC P17655; Q9Y4K0: LOXL2; NbExp=2; IntAct=EBI-1028956, EBI-7172227; CC P17655; O60356: NUPR1; NbExp=3; IntAct=EBI-1028956, EBI-3908808; CC P17655; P07237: P4HB; NbExp=3; IntAct=EBI-1028956, EBI-395883; CC P17655; P60201-2: PLP1; NbExp=3; IntAct=EBI-1028956, EBI-12188331; CC P17655; O75400-2: PRPF40A; NbExp=3; IntAct=EBI-1028956, EBI-5280197; CC P17655; P62826: RAN; NbExp=3; IntAct=EBI-1028956, EBI-286642; CC P17655; Q9P1I4: ST13; NbExp=3; IntAct=EBI-1028956, EBI-25892254; CC P17655; Q8IUH5: ZDHHC17; NbExp=2; IntAct=EBI-1028956, EBI-524753; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=Translocates to CC the plasma membrane upon Ca(2+) binding. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P17655-1; Sequence=Displayed; CC Name=2; CC IsoId=P17655-2; Sequence=VSP_043027, VSP_043028; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- SIMILARITY: Belongs to the peptidase C2 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH07686.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=AAH11828.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M23254; AAA35645.1; -; mRNA. DR EMBL; AF261089; AAF99682.1; -; mRNA. DR EMBL; AK316211; BAH14582.1; -; mRNA. DR EMBL; AY835586; AAV80421.1; -; Genomic_DNA. DR EMBL; AC096542; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC099065; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC007686; AAH07686.1; ALT_SEQ; mRNA. DR EMBL; BC011828; AAH11828.1; ALT_SEQ; mRNA. DR EMBL; BC021303; AAH21303.1; -; mRNA. DR EMBL; J04700; AAA52760.1; -; Genomic_DNA. DR CCDS; CCDS31035.1; -. [P17655-1] DR CCDS; CCDS53478.1; -. [P17655-2] DR PIR; S10590; CIHUH2. DR RefSeq; NP_001139540.1; NM_001146068.1. [P17655-2] DR RefSeq; NP_001739.2; NM_001748.4. [P17655-1] DR PDB; 1KFU; X-ray; 2.50 A; L=2-700. DR PDB; 1KFX; X-ray; 3.15 A; L=2-700. DR PDB; 2NQA; X-ray; 2.20 A; A/B=48-346. DR PDBsum; 1KFU; -. DR PDBsum; 1KFX; -. DR PDBsum; 2NQA; -. DR AlphaFoldDB; P17655; -. DR SMR; P17655; -. DR BioGRID; 107274; 161. DR ComplexPortal; CPX-2674; M-Calpain complex. DR IntAct; P17655; 77. DR MINT; P17655; -. DR STRING; 9606.ENSP00000295006; -. DR BindingDB; P17655; -. DR ChEMBL; CHEMBL2382; -. DR GuidetoPHARMACOLOGY; 2337; -. DR MEROPS; C02.002; -. DR GlyGen; P17655; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P17655; -. DR MetOSite; P17655; -. DR PhosphoSitePlus; P17655; -. DR SwissPalm; P17655; -. DR BioMuta; CAPN2; -. DR DMDM; 317373596; -. DR CPTAC; CPTAC-468; -. DR CPTAC; CPTAC-469; -. DR jPOST; P17655; -. DR MassIVE; P17655; -. DR PaxDb; 9606-ENSP00000295006; -. DR PeptideAtlas; P17655; -. DR ProteomicsDB; 53499; -. [P17655-1] DR ProteomicsDB; 53500; -. [P17655-2] DR Pumba; P17655; -. DR Antibodypedia; 20748; 437 antibodies from 38 providers. DR DNASU; 824; -. DR Ensembl; ENST00000295006.6; ENSP00000295006.5; ENSG00000162909.18. [P17655-1] DR Ensembl; ENST00000433674.6; ENSP00000413158.2; ENSG00000162909.18. [P17655-2] DR GeneID; 824; -. DR KEGG; hsa:824; -. DR MANE-Select; ENST00000295006.6; ENSP00000295006.5; NM_001748.5; NP_001739.3. DR UCSC; uc001hob.5; human. [P17655-1] DR AGR; HGNC:1479; -. DR CTD; 824; -. DR DisGeNET; 824; -. DR GeneCards; CAPN2; -. DR HGNC; HGNC:1479; CAPN2. DR HPA; ENSG00000162909; Low tissue specificity. DR MIM; 114230; gene. DR neXtProt; NX_P17655; -. DR OpenTargets; ENSG00000162909; -. DR PharmGKB; PA26060; -. DR VEuPathDB; HostDB:ENSG00000162909; -. DR eggNOG; KOG0045; Eukaryota. DR GeneTree; ENSGT00940000154784; -. DR HOGENOM; CLU_010982_0_0_1; -. DR InParanoid; P17655; -. DR OMA; ELNLVNW; -. DR OrthoDB; 142935at2759; -. DR PhylomeDB; P17655; -. DR TreeFam; TF314748; -. DR BRENDA; 3.4.22.53; 2681. DR PathwayCommons; P17655; -. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-8862803; Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models. DR SignaLink; P17655; -. DR SIGNOR; P17655; -. DR BioGRID-ORCS; 824; 17 hits in 1154 CRISPR screens. DR ChiTaRS; CAPN2; human. DR EvolutionaryTrace; P17655; -. DR GeneWiki; CAPN2; -. DR GenomeRNAi; 824; -. DR Pharos; P17655; Tchem. DR PRO; PR:P17655; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P17655; protein. DR Bgee; ENSG00000162909; Expressed in bronchial epithelial cell and 207 other cell types or tissues. DR ExpressionAtlas; P17655; baseline and differential. DR GO; GO:0110158; C:calpain complex; IPI:ComplexPortal. DR GO; GO:0000785; C:chromatin; IEA:Ensembl. DR GO; GO:0030864; C:cortical actin cytoskeleton; TAS:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:BHF-UCL. DR GO; GO:0005764; C:lysosome; IEA:Ensembl. DR GO; GO:0045121; C:membrane raft; IDA:BHF-UCL. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IEA:Ensembl. DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0031143; C:pseudopodium; IDA:BHF-UCL. DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl. DR GO; GO:0004198; F:calcium-dependent cysteine-type endopeptidase activity; IDA:BHF-UCL. DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc. DR GO; GO:0008092; F:cytoskeletal protein binding; NAS:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl. DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISS:UniProtKB. DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0007565; P:female pregnancy; IEA:Ensembl. DR GO; GO:0007520; P:myoblast fusion; IEA:Ensembl. DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl. DR GO; GO:1901741; P:positive regulation of myoblast fusion; IEA:Ensembl. DR GO; GO:2001247; P:positive regulation of phosphatidylcholine biosynthetic process; IEA:Ensembl. DR GO; GO:0016540; P:protein autoprocessing; IEA:Ensembl. DR GO; GO:0140249; P:protein catabolic process at postsynapse; IEA:Ensembl. DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB. DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IDA:BHF-UCL. DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:BHF-UCL. DR GO; GO:0032675; P:regulation of interleukin-6 production; IEA:Ensembl. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl. DR CDD; cd00214; Calpain_III; 1. DR CDD; cd00044; CysPc; 1. DR CDD; cd16199; EFh_PEF_CAPN2; 1. DR FunFam; 2.60.120.380:FF:000001; Calpain-1 catalytic subunit; 1. DR FunFam; 3.90.70.10:FF:000001; Calpain-1 catalytic subunit; 1. DR FunFam; 1.10.238.10:FF:000099; calpain-2 catalytic subunit; 1. DR Gene3D; 2.60.120.380; -; 1. DR Gene3D; 3.90.70.10; Cysteine proteinases; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR033883; C2_III. DR InterPro; IPR050420; Calpain. DR InterPro; IPR022684; Calpain_cysteine_protease. DR InterPro; IPR022682; Calpain_domain_III. DR InterPro; IPR022683; Calpain_III. DR InterPro; IPR036213; Calpain_III_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR042736; EFh_PEF_CAPN2. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR000169; Pept_cys_AS. DR InterPro; IPR001300; Peptidase_C2_calpain_cat. DR PANTHER; PTHR10183; CALPAIN; 1. DR PANTHER; PTHR10183:SF268; CALPAIN-2 CATALYTIC SUBUNIT; 1. DR Pfam; PF01067; Calpain_III; 1. DR Pfam; PF13833; EF-hand_8; 1. DR Pfam; PF00648; Peptidase_C2; 1. DR PRINTS; PR00704; CALPAIN. DR SMART; SM00720; calpain_III; 1. DR SMART; SM00230; CysPc; 1. DR SUPFAM; SSF49758; Calpain large subunit, middle domain (domain III); 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS50203; CALPAIN_CAT; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 3. DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Calcium; Cell membrane; KW Cytoplasm; Direct protein sequencing; Hydrolase; Membrane; Metal-binding; KW Protease; Proteomics identification; Reference proteome; Repeat; KW Thiol protease. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0007744|PubMed:22814378" FT PROPEP 2..19 FT /note="Anchors to the small subunit" FT /evidence="ECO:0000255" FT /id="PRO_0000026487" FT CHAIN 20..700 FT /note="Calpain-2 catalytic subunit" FT /id="PRO_0000026488" FT DOMAIN 45..344 FT /note="Calpain catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00239" FT DOMAIN 572..605 FT /note="EF-hand 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 602..637 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 667..700 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION 345..514 FT /note="Domain III" FT REGION 515..529 FT /note="Linker" FT REGION 530..700 FT /note="Domain IV" FT ACT_SITE 105 FT /evidence="ECO:0000250" FT ACT_SITE 262 FT /evidence="ECO:0000250" FT ACT_SITE 286 FT /evidence="ECO:0000250" FT BINDING 89 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 91 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 96 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 175 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="3" FT /evidence="ECO:0000250" FT BINDING 229 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 230 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 292 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 299 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 323 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="4" FT /evidence="ECO:0000250" FT BINDING 542 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 545 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 547 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 552 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="5" FT /evidence="ECO:0000250" FT BINDING 585 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 587 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 589 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 591 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 596 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 615 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 617 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 619 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 621 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 626 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="7" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 658 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 661 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT VAR_SEQ 1..78 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043027" FT VAR_SEQ 79 FT /note="T -> M (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_043028" FT VARIANT 22 FT /note="D -> E (in dbSNP:rs25655)" FT /evidence="ECO:0000269|PubMed:10944468, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2539381, FT ECO:0000269|PubMed:2852952, ECO:0000269|Ref.4, FT ECO:0007744|PubMed:21269460" FT /id="VAR_014435" FT VARIANT 68 FT /note="S -> G (in dbSNP:rs2230083)" FT /evidence="ECO:0000269|PubMed:2539381, ECO:0000269|Ref.4" FT /id="VAR_021404" FT VARIANT 476 FT /note="K -> R (in dbSNP:rs9804140)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_021405" FT VARIANT 521 FT /note="E -> Q (in dbSNP:rs28370127)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_021406" FT VARIANT 568 FT /note="K -> Q (in dbSNP:rs17599)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_014436" FT VARIANT 677 FT /note="K -> Q (in dbSNP:rs2230082)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_021407" FT CONFLICT 73..74 FT /note="IE -> MR (in Ref. 1; AAA35645)" FT /evidence="ECO:0000305" FT CONFLICT 256 FT /note="Q -> K (in Ref. 2; AAF99682)" FT /evidence="ECO:0000305" FT CONFLICT 300 FT /note="N -> S (in Ref. 2; AAF99682)" FT /evidence="ECO:0000305" FT CONFLICT 534 FT /note="F -> V (in Ref. 1; AAA35645 and 2; AAF99682)" FT /evidence="ECO:0000305" FT HELIX 4..16 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 17..19 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 32..42 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 55..58 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 60..68 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 74..76 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 78..81 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:1KFX" FT HELIX 94..96 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 97..99 FT /evidence="ECO:0007829|PDB:1KFX" FT HELIX 105..115 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 131..134 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 136..144 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 146..155 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 158..161 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 164..167 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 169..175 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 177..189 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 190..192 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 196..199 FT /evidence="ECO:0007829|PDB:2NQA" FT TURN 204..206 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 207..209 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 224..233 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 237..241 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 247..249 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 259..261 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 264..274 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 277..285 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 294..297 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 299..301 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 302..306 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 309..315 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 321..327 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 328..334 FT /evidence="ECO:0007829|PDB:2NQA" FT STRAND 336..341 FT /evidence="ECO:0007829|PDB:2NQA" FT HELIX 344..346 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 347..349 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 363..365 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 367..370 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 378..380 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 381..383 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 388..390 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 400..402 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 406..413 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 420..425 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 429..435 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 442..444 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 450..455 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 459..461 FT /evidence="ECO:0007829|PDB:1KFX" FT STRAND 466..471 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 474..476 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 479..492 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 495..505 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 507..509 FT /evidence="ECO:0007829|PDB:1KFX" FT STRAND 527..530 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 533..541 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 542..546 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 550..560 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 561..564 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 574..582 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 586..588 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 590..592 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 595..612 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 622..624 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 627..630 FT /evidence="ECO:0007829|PDB:1KFU" FT TURN 631..635 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 640..650 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 655..657 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 659..679 FT /evidence="ECO:0007829|PDB:1KFU" FT STRAND 687..690 FT /evidence="ECO:0007829|PDB:1KFU" FT HELIX 691..698 FT /evidence="ECO:0007829|PDB:1KFU" SQ SEQUENCE 700 AA; 79995 MW; 8CF8294351A024E3 CRC64; MAGIAAKLAK DREAAEGLGS HDRAIKYLNQ DYEALRNECL EAGTLFQDPS FPAIPSALGF KELGPYSSKT RGIEWKRPTE ICADPQFIIG GATRTDICQG ALGDCWLLAA IASLTLNEEI LARVVPLNQS FQENYAGIFH FQFWQYGEWV EVVVDDRLPT KDGELLFVHS AEGSEFWSAL LEKAYAKING CYEALSGGAT TEGFEDFTGG IAEWYELKKP PPNLFKIIQK ALQKGSLLGC SIDITSAADS EAITFQKLVK GHAYSVTGAE EVESNGSLQK LIRIRNPWGE VEWTGRWNDN CPSWNTIDPE ERERLTRRHE DGEFWMSFSD FLRHYSRLEI CNLTPDTLTS DTYKKWKLTK MDGNWRRGST AGGCRNYPNT FWMNPQYLIK LEEEDEDEED GESGCTFLVG LIQKHRRRQR KMGEDMHTIG FGIYEVPEEL SGQTNIHLSK NFFLTNRARE RSDTFINLRE VLNRFKLPPG EYILVPSTFE PNKDGDFCIR VFSEKKADYQ AVDDEIEANL EEFDISEDDI DDGFRRLFAQ LAGEDAEISA FELQTILRRV LAKRQDIKSD GFSIETCKIM VDMLDSDGSG KLGLKEFYIL WTKIQKYQKI YREIDVDRSG TMNSYEMRKA LEEAGFKMPC QLHQVIVARF ADDQLIIDFD NFVRCLVRLE TLFKIFKQLD PENTGTIELD LISWLCFSVL //